KEGG ORTHOLOGY: K12927

ORTHOLOGY: K12927

Entry

K12927            Tight     KO

Symbol

AG22

Name

abietadiene/neoabietadiene/copalyl diphosphate synthase [EC:4.2.3.18 4.2.3.132 5.5.1.12]

Pathway

map00904

Diterpenoid biosynthesis

map01100

Metabolic pathways

map01110

Biosynthesis of secondary metabolites

Reaction

R06298

(+)-copalyl-diphosphate lyase (decyclizing)

R06301

(+)-copalyl-diphosphate diphosphate-lyase [cyclizing, abieta-7,13-diene-forming]

R06303

(+)-copaly-diphosphate diphosphate-lyase (cyclizing, neoabietadiene-forming)

Brite

KEGG Orthology (KO) [BR:ko00001]
09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K12927  AG22; abietadiene/neoabietadiene/copalyl diphosphate synthase
Enzymes [BR:ko01000]
4. Lyases
  4.2  Carbon-oxygen lyases
   4.2.3  Acting on phosphates
    4.2.3.18  abieta-7,13-diene synthase
     K12927  AG22; abietadiene/neoabietadiene/copalyl diphosphate synthase
    4.2.3.132  neoabietadiene synthase
     K12927  AG22; abietadiene/neoabietadiene/copalyl diphosphate synthase
5. Isomerases
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12  copalyl diphosphate synthase
     K12927  AG22; abietadiene/neoabietadiene/copalyl diphosphate synthase

Other DBs

GO:	0050554 0050559

Genes

AG:	AAB05407(AG22)

Reference

PMID:11552804

Authors

Peters RJ1, Ravn MM, Coates RM, Croteau RB

Title

Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites.

Journal

J Am Chem Soc 123:8974-8 (2001)
DOI:10.1021/ja010670k

Sequence

[ag:AAB05407]

LinkDB

ORTHOLOGY: K14041

Entry

K14041            Tight     KO

Symbol

TPS-LAS, LPS

Name

levopimaradiene/copalyl diphosphate synthase [EC:4.2.3.32 5.5.1.12]

Pathway

map00904

Diterpenoid biosynthesis

map01100

Metabolic pathways

map01110

Biosynthesis of secondary metabolites

Reaction

R06298

(+)-copalyl-diphosphate lyase (decyclizing)

R06302

(+)-copalyl-diphosphate diphosphate-lyase [abieta-8(14),12-diene-forming]

R06304

(+)-copalyl-diphosphate diphosphate-lyase (palustradiene-forming)

Brite

KEGG Orthology (KO) [BR:ko00001]
09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K14041  TPS-LAS, LPS; levopimaradiene/copalyl diphosphate synthase
Enzymes [BR:ko01000]
4. Lyases
  4.2  Carbon-oxygen lyases
   4.2.3  Acting on phosphates
    4.2.3.32  levopimaradiene synthase
     K14041  TPS-LAS, LPS; levopimaradiene/copalyl diphosphate synthase
5. Isomerases
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12  copalyl diphosphate synthase
     K14041  TPS-LAS, LPS; levopimaradiene/copalyl diphosphate synthase

Other DBs

GO:	0052678 0050559

Genes

AG:	AAL09965(LPS)

Reference

PMID:11488601

Authors

Schepmann HG, Pang J, Matsuda SP

Title

Cloning and characterization of Ginkgo biloba levopimaradiene synthase which catalyzes the first committed step in ginkgolide biosynthesis.

Journal

Arch Biochem Biophys 392:263-9 (2001)
DOI:10.1006/abbi.2001.2438

Sequence

[ag:AAL09965]

Reference

PMID:18198275

Authors

Keeling CI, Weisshaar S, Lin RP, Bohlmann J

Title

Functional plasticity of paralogous diterpene synthases involved in conifer defense.

Journal

Proc Natl Acad Sci U S A 105:1085-90 (2008)
DOI:10.1073/pnas.0709466105

Reference

PMID:15310829

Authors

Martin DM, Faldt J, Bohlmann J

Title

Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily.

Journal

Plant Physiol 135:1908-27 (2004)
DOI:10.1104/pp.104.042028

LinkDB

ORTHOLOGY: K19571

Entry

K19571            Tight     KO

Symbol

LPS

Name

levopimaradiene/neoabietadiene/copalyl diphosphate synthase [EC:4.2.3.32 4.2.3.132 5.5.1.12]

Pathway

map00904

Diterpenoid biosynthesis

map01110

Biosynthesis of secondary metabolites

Reaction

R06298

(+)-copalyl-diphosphate lyase (decyclizing)

R06302

(+)-copalyl-diphosphate diphosphate-lyase [abieta-8(14),12-diene-forming]

R06303

(+)-copaly-diphosphate diphosphate-lyase (cyclizing, neoabietadiene-forming)

R06304

(+)-copalyl-diphosphate diphosphate-lyase (palustradiene-forming)

Brite

KEGG Orthology (KO) [BR:ko00001]
09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K19571  LPS; levopimaradiene/neoabietadiene/copalyl diphosphate synthase
Enzymes [BR:ko01000]
4. Lyases
  4.2  Carbon-oxygen lyases
   4.2.3  Acting on phosphates
    4.2.3.32  levopimaradiene synthase
     K19571  LPS; levopimaradiene/neoabietadiene/copalyl diphosphate synthase
    4.2.3.132  neoabietadiene synthase
     K19571  LPS; levopimaradiene/neoabietadiene/copalyl diphosphate synthase
5. Isomerases
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12  copalyl diphosphate synthase
     K19571  LPS; levopimaradiene/neoabietadiene/copalyl diphosphate synthase

Other DBs

GO:	0052678 0050559

Genes

AG:	AAX07435(LPS)

Reference

PMID:16497345

Authors

Ro DK, Bohlmann J

Title

Diterpene resin acid biosynthesis in loblolly pine (Pinus taeda): functional characterization of abietadiene/levopimaradiene synthase (PtTPS-LAS) cDNA and subcellular targeting of PtTPS-LAS and abietadienol/abietadienal oxidase (PtAO, CYP720B1).

Journal

Phytochemistry 67:1572-8 (2006)
DOI:10.1016/j.phytochem.2006.01.011

Sequence

[ag:AAX07435]

LinkDB

ORTHOLOGY: K14042

Entry

K14042            Tight     KO

Symbol

TPS-ISO

Name

isopimara-7,15-diene synthase /copalyl diphosphate synthase [EC:4.2.3.44 5.5.1.12]

Pathway

map00904

Diterpenoid biosynthesis

map01100

Metabolic pathways

map01110

Biosynthesis of secondary metabolites

Reaction

R06298

(+)-copalyl-diphosphate lyase (decyclizing)

R09111

(+)-copalyl diphosphate-lyase (isopimara-7,15-diene-forming)

Brite

KEGG Orthology (KO) [BR:ko00001]
09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K14042  TPS-ISO; isopimara-7,15-diene synthase /copalyl diphosphate synthase
Enzymes [BR:ko01000]
4. Lyases
  4.2  Carbon-oxygen lyases
   4.2.3  Acting on phosphates
    4.2.3.44  isopimara-7,15-diene synthase
     K14042  TPS-ISO; isopimara-7,15-diene synthase /copalyl diphosphate synthase
5. Isomerases
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12  copalyl diphosphate synthase
     K14042  TPS-ISO; isopimara-7,15-diene synthase /copalyl diphosphate synthase

Other DBs

GO:

0050559

Genes

AG:	AAS47690(TPS-ISO)

Reference

PMID:15310829

Authors

Martin DM, Faldt J, Bohlmann J

Title

Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily.

Journal

Plant Physiol 135:1908-27 (2004)
DOI:10.1104/pp.104.042028

Sequence

[ag:AAS47690]

Reference

PMID:18052062

Authors

Wilderman PR, Peters RJ

Title

A single residue switch converts abietadiene synthase into a pimaradiene specific cyclase.

Journal

J Am Chem Soc 129:15736-7 (2007)
DOI:10.1021/ja074977g

LinkDB

ORTHOLOGY: K18113

Entry

K18113            Tight     KO

Symbol

MDS

Name

miltiradiene synthase / copalyl diphosphate synthase [EC:4.2.3.131 5.5.1.12]

Pathway

map00904

Diterpenoid biosynthesis

map01100

Metabolic pathways

map01110

Biosynthesis of secondary metabolites

Reaction

R06298

(+)-copalyl-diphosphate lyase (decyclizing)

R10585

(+)-copaly-diphosphate diphosphate-lyase (cyclizing, miltiradiene-forming)

Brite

KEGG Orthology (KO) [BR:ko00001]
09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K18113  MDS; miltiradiene synthase / copalyl diphosphate synthase
Enzymes [BR:ko01000]
4. Lyases
  4.2  Carbon-oxygen lyases
   4.2.3  Acting on phosphates
    4.2.3.131  miltiradiene synthase
     K18113  MDS; miltiradiene synthase / copalyl diphosphate synthase
5. Isomerases
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12  copalyl diphosphate synthase
     K18113  MDS; miltiradiene synthase / copalyl diphosphate synthase

Other DBs

GO:

0050559

Genes

SMO:	SELMODRAFT_450918

Reference

PMID:22027823

Authors

Sugai Y, Ueno Y, Hayashi K, Oogami S, Toyomasu T, Matsumoto S, Natsume M, Nozaki H, Kawaide H

Title

Enzymatic (13)C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii.

Journal

J Biol Chem 286:42840-7 (2011)
DOI:10.1074/jbc.M111.302703

Sequence

[smo:SELMODRAFT_450918]

LinkDB

ORTHOLOGY: K20514

Entry

K20514            Tight     KO

Symbol

DC1

Name

phyllocladan-16alpha-ol/copalyl diphosphate synthase [EC:4.2.3.45 5.5.1.12]

Pathway

map00904

Diterpenoid biosynthesis

map01110

Biosynthesis of secondary metabolites

Reaction

R06298

(+)-copalyl-diphosphate lyase (decyclizing)

R09686

(+)-copalyl-diphosphate diphosphate-lyase (phyllocladan-16alpha-ol-forming)

Brite

KEGG Orthology (KO) [BR:ko00001]
09100 Metabolism
  09109 Metabolism of terpenoids and polyketides
   00904 Diterpenoid biosynthesis
    K20514  DC1; phyllocladan-16alpha-ol/copalyl diphosphate synthase
Enzymes [BR:ko01000]
4. Lyases
  4.2  Carbon-oxygen lyases
   4.2.3  Acting on phosphates
    4.2.3.45  phyllocladan-16alpha-ol synthase
     K20514  DC1; phyllocladan-16alpha-ol/copalyl diphosphate synthase
5. Isomerases
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12  copalyl diphosphate synthase
     K20514  DC1; phyllocladan-16alpha-ol/copalyl diphosphate synthase

Other DBs

GO:

0050559

Genes

AG:	BAG30961(PaDC1)

Reference

PMID:18391465

Authors

Toyomasu T, Niida R, Kenmoku H, Kanno Y, Miura S, Nakano C, Shiono Y, Mitsuhashi W, Toshima H, Oikawa H, Hoshino T, Dairi T, Kato N, Sassa T

Title

Identification of diterpene biosynthetic gene clusters and functional analysis of labdane-related diterpene cyclases in Phomopsis amygdali.

Journal

Biosci Biotechnol Biochem 72:1038-47 (2008)
DOI:10.1271/bbb.70790

Sequence

[ag:BAG30961]

LinkDB

ENZYME: 5.5.1.12

Entry

EC 5.5.1.12                 Enzyme

Name

copalyl diphosphate synthase;
(+)-copalyl-diphosphate lyase (decyclizing)

Class

Isomerases;
Intramolecular lyases;
Intramolecular lyases (only sub-subclass identified to date)

Sysname

(+)-copalyl-diphosphate lyase (ring-opening)

Reaction(IUBMB)

geranylgeranyl diphosphate = (+)-copalyl diphosphate [RN:R06298]

Reaction(KEGG)

R06298

Substrate

geranylgeranyl diphosphate [CPD:C00353]

Product

(+)-copalyl diphosphate [CPD:C11901]

Comment

In some plants, such as Salvia miltiorrhiza, this enzyme is monofunctional. In other plants this activity is often a part of a bifunctional enzyme. For example, in Selaginella moellendorffii this activity is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.131, miltiradiene synthase, while in the tree Abies grandis (grand fir) it is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.18, abietadiene synthase.

History

EC 5.5.1.12 created 2002, modified 2012

Pathway

ec00904

Diterpenoid biosynthesis

ec01100

Metabolic pathways

ec01110

Biosynthesis of secondary metabolites

Orthology

K12927

abietadiene/neoabietadiene/copalyl diphosphate synthase

K14041

levopimaradiene/copalyl diphosphate synthase

K14042

isopimara-7,15-diene synthase /copalyl diphosphate synthase

K18113

miltiradiene synthase / copalyl diphosphate synthase

K19571

levopimaradiene/neoabietadiene/copalyl diphosphate synthase

K20514

phyllocladan-16alpha-ol/copalyl diphosphate synthase

Genes

SMO:	SELMODRAFT_450918

Reference

1 [PMID:11552804]

Authors

Peters RJ1, Ravn MM, Coates RM, Croteau RB

Title

Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites.

Journal

J Am Chem Soc 123:8974-8 (2001)
DOI:10.1021/ja010670k

Sequence

[ag:AAB05407]

Reference

2 [PMID:22027823]

Authors

Sugai Y, Ueno Y, Hayashi K, Oogami S, Toyomasu T, Matsumoto S, Natsume M, Nozaki H, Kawaide H

Title

Enzymatic (13)C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii.

Journal

J Biol Chem 286:42840-7 (2011)
DOI:10.1074/jbc.M111.302703

Sequence

[smo:SELMODRAFT_450918]

Reference

3 [PMID:11805316]

Authors

Peters RJ, Croteau RB.

Title

Abietadiene synthase catalysis: mutational analysis of a prenyl diphosphate ionization-initiated cyclization and rearrangement.

Journal

Proc Natl Acad Sci U S A 99:580-4 (2002)
DOI:10.1073/pnas.022627099

Sequence

[ag:AAB05407]

Reference

4 [PMID:12059223]

Authors

Ravn MM, Peters RJ, Coates RM, Croteau R.

Title

Mechanism of abietadiene synthase catalysis: stereochemistry and stabilization of the cryptic pimarenyl carbocation intermediates.

Journal

J Am Chem Soc 124:6998-7006 (2002)
DOI:10.1021/ja017734b

Reference

5 [PMID:11827528]

Authors

Peters RJ, Croteau RB.

Title

Abietadiene synthase catalysis: conserved residues involved in protonation-initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate.

Journal

Biochemistry 41:1836-42 (2002)
DOI:10.1021/bi011879d

Sequence

[ag:AAB05407]

Other DBs

ExplorEnz - The Enzyme Database:

5.5.1.12

IUBMB Enzyme Nomenclature:

5.5.1.12

ExPASy - ENZYME nomenclature database:

5.5.1.12

BRENDA, the Enzyme Database:

5.5.1.12

CAS:	157972-08-2

LinkDB

REACTION: R06298

Entry

R06298                      Reaction

Name

(+)-copalyl-diphosphate lyase (decyclizing)

Definition

Geranylgeranyl diphosphate <=> Copalyl diphosphate

Equation

C00353 <=> C11901

Reaction class

RC00642

C00353_C11901

Enzyme

5.5.1.12

Pathway

rn00904

Diterpenoid biosynthesis

rn01100

Metabolic pathways

rn01110

Biosynthesis of secondary metabolites

Brite

Enzymatic reactions [BR:br08201]
5. Isomerase reactions
  5.5  Intramolecular lyases
   5.5.1  Intramolecular lyases (only sub-subclass identified to date)
    5.5.1.12
     R06298  Geranylgeranyl diphosphate <=> Copalyl diphosphate

Orthology

K12927

abietadiene/neoabietadiene/copalyl diphosphate synthase [EC:4.2.3.18 4.2.3.132 5.5.1.12]

K14041

levopimaradiene/copalyl diphosphate synthase [EC:4.2.3.32 5.5.1.12]

K14042

isopimara-7,15-diene synthase /copalyl diphosphate synthase [EC:4.2.3.44 5.5.1.12]

K18113

miltiradiene synthase / copalyl diphosphate synthase [EC:4.2.3.131 5.5.1.12]

K19571

levopimaradiene/neoabietadiene/copalyl diphosphate synthase [EC:4.2.3.32 4.2.3.132 5.5.1.12]

K20514

phyllocladan-16alpha-ol/copalyl diphosphate synthase [EC:4.2.3.45 5.5.1.12]

Other DBs

RHEA:

24319

LinkDB

DBGET integrated database retrieval system